Multilayer processing devices and methods

ABSTRACT

Sample processing devices that include transmissive layers and control layers to reduce or eliminate cross-talk between process chambers in the processing device are disclosed. The transmissive layers may transmit significant portions of signal light and/or interrogation light while the control layers block significant portions of signal light and/or interrogation light. Methods of manufacturing processing devices that include transmissive layers and control layers are also disclosed. The methods may involve continuous forming processes including co-extrusion of materials to form the transmissive layer and control layer in a processing device, followed by formation of the process chambers in the control layer. Alternatively, the methods may involve extrusion of materials for the control layer, followed by formation of process chambers in the control layer.

BACKGROUND

A variety of devices have been designed for the simultaneous processingof chemical, biochemical, and other reactions. The devices typicallyinclude a number of wells or process chambers in which the processing isperformed. Detection of various analytes or process products may beperformed by detecting signal light emitted from the process chambers.The signal light may be caused by, e.g., reactions within the processchambers. In other instances, the signal light may be in response toexcitation by interrogating light directed into the process chamber froman external source (e.g., a laser, etc.), where the signal light resultsfrom, e.g., chemiluminescence, etc.

Regardless of the mechanism or technique used to cause the emission ofsignal light from the process chambers, its detection and correlation tospecific process chambers may be required. If, for example, the signallight emitted from one process chamber is attributed to a differentprocess chamber, erroneous test results may result. The phenomenon ofsignal light emitted from a first process chamber and transmitted to asecond process chamber is commonly referred to as “cross-talk.”Cross-talk can lead to erroneous results when, for example, the secondprocess chamber would not emit any signal light alone, but the signallight transmitted to the second process chamber from the first processchamber is detected and recorded as a false positive result.

Attempts to avoid cross-talk may include increasing the distance betweenthe process chambers such that any signal light reaching the secondprocess chamber is too weak to register as a positive result with adetector. Other approaches include masking or shrouding the processchambers using an external device located over the process chambers suchas is described in International Publication No. WO 02/01180 A2(Bedingham et al.). One problem with these approaches is that processchamber density on a device may be limited, resulting in a less thandesired number of tests being performed on a given sample processingdevice. Another potential problem with these approaches is that theyrequire the use of articles or materials (e.g., masks, shrouds, etc.) inaddition to the sample processing devices, thus increasing the cost andcomplexity of using the sample processing devices.

Another situation in which the issue of isolation between processchambers from cross-talk may arise in the delivery of interrogatinglight to the process chambers. For example, it may be desired that notall of the process chambers be interrogated at the same time. In otherwords, the process chambers may be interrogated serially (i.e., one at atime) or only selected groups of process chambers may be interrogated atthe same time. In such a situation, it may be preferred that none orlimited amounts of the interrogating light be transmitted to the processchambers that are not the subject of interrogation. With knownprocessing devices, the control over interrogating light may require theuse of masks or shrouds, thus raising the same problems of limitedprocess chamber density, as well as the cost and complexity added by theadditional articles/process steps.

Other problems associated with processing devices include control overthe feature size, shape, and location. For example, it may be desiredthat variations in process chamber sizes, shapes, locations, etc., aswell as the size, shape and location of other features in the devices(e.g., delivery conduits, loading chambers, etc.) be limited. Variationsin feature size may detrimentally affect test accuracy by, e.g.,changing the volume of analyte in the different process chambers.Further, variations in feature size may require additional sample volumeto, e.g., ensure filling of all process chambers, etc. Variations infeature shape may, e.g., affect the signal light density emitted from aprocess chamber. Variations in feature location may, e.g., reduce testaccuracy if process chamber location is not repeatable between differentprocessing devices.

SUMMARY

The present invention provides sample processing devices that includetransmissive layers and control layers to reduce or eliminate cross-talkbetween process chambers in the processing device. The transmissivelayers preferably transmit significant portions of signal light and/orinterrogation light while the control layers block significant portionsof signal light and/or interrogation light.

The present invention also provides methods of manufacturing processingdevices that include transmissive layers and control layers. The methodsmay, in some embodiments, involve continuous forming processes includingco-extrusion of materials to form the transmissive layer and controllayer in a processing device, followed by formation of the processchambers in the control layer. In other embodiments, the methods mayinvolve extrusion of materials for the control layer, followed byformation of process chambers in the control layer.

The control layers used in processing devices and methods of the presentinvention are provided to block the transmission of selected light wherethe “selected light” may be light of one or more particular wavelengths,one or more ranges of wavelengths, one or more polarization states, orcombinations thereof. As used in connection with the present invention,“blocking” of light involves one or more of absorption, reflection,refraction, or diffusion of the selected light. In the case of signallight, transmission of the signal light through the control layer ispreferably prevented or reduced to levels that will not result in falsepositive readings from process chambers. In the case of interrogationlight, transmission of the interrogation light through the control layeris preferably prevented or reduced to levels that will not result inunwanted interrogation of process chambers. The control layers may blocklight of selected wavelengths or ranges of wavelengths. The controllayers may also block light of one or more selected polarization states(e.g., s polarization, p polarization, circular polarization, etc).

As used in connection with the present invention, the term “light” willbe used to refer to electromagnetic energy, whether visible to the humaneye or not. It may be preferred that the light fall within a range ofultraviolet to infrared electromagnetic energy, and, in some instances,it may be preferred that light include electromagnetic energy in thespectrum visible to the human eye.

The processing devices of the present invention may provide a number ofpotential advantages. For example, by blocking the transmission ofsignal light, cross-talk during emission of signal light can be reducedor eliminated. With respect to the delivery of interrogation light,blocking the transmission of interrogation light to selected processchambers can reduce or eliminate unwanted interrogation of the selectedprocess chambers.

Furthermore, the methods of the present invention may provide for fastand economical manufacturing of processing devices including bothtransmissive layers and control layers. Further, the methods may provideprocessing devices including features (e.g., process chambers,distribution conduits, etc.) that are accurately sized shaped andlocated.

In one aspect, the present invention provides a sample processing deviceincluding a body with a transmissive layer that transmits selected lightand a control layer that blocks the selected light, wherein the controllayer is attached to the transmissive layer with a first major surfaceof the control layer facing the transmissive layer and a second majorsurface facing away from the transmissive layer; a plurality of processchamber structures formed in the control layer, wherein each of theprocess chamber structures includes an interior window surface and aninterior side surface formed by the control layer; a cover sheetattached to the second major surface of the control layer, wherein thecover sheet and the plurality of process chamber structures define aplurality of process chambers in the sample processing device, whereinthe selected light can be transmitted into or out of each processchamber through the interior window surface; and a conduit in the sampleprocessing device, wherein each process chamber of the plurality ofprocess chambers is in fluid communication with the conduit.

In another aspect, the present invention provides a sample processingdevice including a body with a transmissive layer that transmitsselected light and a control layer that blocks the selected light,wherein a first major surface of the control layer faces and ismelt-bonded to the transmissive layer, and wherein a second majorsurface of the control layer faces away from the transmissive layer; aplurality of process chamber structures formed in the body, wherein eachof the process chamber structures includes a void formed through thefirst major surface and the second major surface of the control layer,wherein the void exposes an interior window surface formed by thetransmissive layer within each process chamber structure; a cover sheetattached to the second major surface of the control layer, wherein thecover sheet and the plurality of process chamber structures define aplurality of process chambers in the sample processing device, andwherein the cover sheet blocks the selected light; and a conduit formedbetween the cover sheet and the control layer in the sample processingdevice, wherein each process chamber of the plurality of processchambers is in fluid communication with the conduit.

In another aspect, the present invention provides a method ofmanufacturing a sample processing device, the method including providinga body that includes a transmissive layer that transmits selected light;a control layer that blocks the selected light, wherein the controllayer is attached to the transmissive layer with a first major surfaceof the control layer facing the transmissive layer and a second majorsurface facing away from the transmissive layer; a plurality of processchamber structures formed in the control layer, wherein each of theprocess chamber structures includes an interior window surface and aninterior side surface formed by the control layer; and attaching a coversheet to the second major surface of the control layer, wherein thecover sheet and the plurality of process chamber structures define aplurality of process chambers in the sample processing device, andwherein attaching the cover sheet forms a conduit in the sampleprocessing device, wherein each process chamber of the plurality ofprocess chambers is in fluid communication with the conduit.

In another aspect, the present invention provides a sample processingdevice including a body with a first major surface and a second majorsurface, wherein the second major surface is flat, and wherein the bodyblocks selected light; a plurality of process chamber structures formedin the body, wherein the process chamber structures are formed into thefirst major surface of the body; a cover sheet attached to the firstmajor surface of the body, wherein the cover sheet and the plurality ofprocess chamber structures define a plurality of process chambers in thesample processing device, and wherein the cover sheet transmits theselected light; and a conduit located between the body and the coversheet, wherein each process chamber of the plurality of process chambersis in fluid communication with the conduit.

In another aspect, the present invention provides a method ofmanufacturing a sample processing device, the method including providinga body that includes a first major surface and a second major surface,wherein the second major surface is flat, and wherein the body blocksselected light, wherein the body further includes a plurality of processchamber structures formed in the first major surface of the body; andattaching a cover sheet to the first major surface of the body, whereinthe cover sheet and the plurality of process chamber structures define aplurality of process chambers in the sample processing device; andwherein attaching the cover sheet forms a conduit in the sampleprocessing device, wherein each process chamber of the plurality ofprocess chambers is in fluid communication with the conduit.

These and other features and advantages may be described below inconnection with various illustrative embodiments of the invention.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a perspective view of one illustrative processing deviceaccording to the present invention with the cover removed to expose thestructures formed therein.

FIG. 2 is an enlarged view of a portion of the processing device of FIG.1.

FIG. 3 is a cross-sectional view of FIG. 2 taken along line 3-3 in FIG.2, with the cover located thereon.

FIG. 4 is a cross-sectional view of an alternative processing deviceaccording to the present invention.

FIG. 5 is a schematic diagram of a portion of one manufacturing processaccording to the present invention.

FIG. 6 is a schematic diagram of a system for manufacturing processingdevices according to the present invention.

FIG. 7 is a schematic diagram of a portion of another manufacturingprocess according to the present invention.

FIG. 8 is a schematic diagram of a system for manufacturing processingdevices according to the present invention.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS OF THE INVENTION

In the following detailed description of illustrative embodiments,reference is made to the accompanying figures of the drawing which forma part hereof, and in which are shown, by way of illustration, specificembodiments in which the invention may be practiced. It is to beunderstood that other embodiments may be utilized and structural changesmay be made without departing from the scope of the present invention.

The present invention provides a sample processing device that can beused in the processing of liquid sample materials (or sample materialsentrained in a liquid) in multiple process chambers to obtain desiredreactions, e.g., PCR amplification, ligase chain reaction (LCR),self-sustaining sequence replication, enzyme kinetic studies,homogeneous ligand binding assays, and other chemical, biochemical, orother reactions that may, e.g., require precise and/or rapid thermalvariations. More particularly, the present invention provides sampleprocessing devices that include one or more process arrays, each ofwhich include a loading chamber, a plurality of process chambers and amain conduit placing the process chambers in fluid communication withthe loading chamber.

Although various constructions of illustrative embodiments are describedbelow, sample processing devices of the present invention may be similarto those described in, e.g., International Publication Nos. WO 02/01180and WO 02/00347 (both to Bedingham et al.). The documents identifiedabove all disclose a variety of different features that could beincorporated into sample processing devices of the present invention.

One illustrative sample processing device manufactured according to theprinciples of the present invention is illustrated in FIGS. 1 & 2, whereFIG. 1 is a perspective view of one sample processing device 10 and FIG.2 is an enlarged plan view of a portion of the sample processing device10. In both views, a cover (described below in connection with FIG. 3)has been removed to expose structures formed in the body 60 of thedevice 10.

The sample processing device 10 includes at least one, and preferably aplurality of process arrays 20. Each of the depicted process arrays 20preferably extends from proximate a first end 12 towards the second end14 of the sample processing device 10. The process arrays 20 aredepicted as being substantially parallel in their arrangement on thesample processing device 10. Although this arrangement may be preferred,it will be understood that any arrangement of process arrays 20 mayalternatively be preferred.

Alignment of the process arrays 20 as depicted may be useful if the mainconduits 40 of the process arrays are to be closed simultaneously asdiscussed in, e.g., International Publication No. WO 02/01180. Alignmentof the process arrays 20 may also be useful if sample materials are tobe distributed throughout the sample processing device by rotation aboutan axis of rotation proximate the first end 12 of the device 10 asdiscussed in, e.g., International Publication No. WO 02/01180.

Each of the process arrays 20 in the depicted embodiment includes atleast one main conduit 40, and a plurality of process chambers 50located along each main conduit 40. The process arrays 20 may alsopreferably include a loading structure in fluid communication with amain conduit 40 to facilitate delivery of sample material to the processchambers 50 through the main conduit 40. It may be preferred that, asdepicted in FIG. 1, each of the process arrays include only one loadingstructure 30 and only one main conduit 40.

The loading structure 30 may be designed to mate with an externalapparatus (e.g., a pipette, hollow syringe, or other fluid deliveryapparatus) to receive the sample material. The loading structure 30itself may define a volume or it may define no specific volume, but,instead, be a location at which sample material is to be introduced. Forexample, the loading structure may be provided in the form of a portthrough which a pipette or needle is to be inserted. In one embodiment,the loading structure may be, e.g., a designated location along the mainconduit that is adapted to receive a pipette, syringe needle, etc. Theloading may be performed manually or by an automated system (e.g.,robotic, etc.). Further, the processing device 10 may be loaded directlyfrom another device (using an automated system or manually).

The loading chamber depicted in FIG. 1 is only one embodiment of aloading structure 30 in fluid communication with the main conduit 40. Itmay be preferred that the loading chamber volume, i.e., the volumedefined by the loading chamber (if so provided), be equal to or greaterthan the combined volume of the main conduit 40, process chambers 50,and feeder conduits 42 (if any).

The process chambers 50 are in fluid communication with the main conduit40 through feeder conduits 42. As a result, the loading structure 30 ineach of the process arrays 20 is in fluid communication with each of theprocess chambers 50 located along the main conduit 40 leading to theloading structure 30. If desired, each of the process arrays 20 may alsoinclude an optional drain chamber (not shown) located at the end of themain conduit 40 opposite the loading structure 30.

FIG. 3 is a cross-sectional view of the portion of the processing device10 depicted in FIG. 2 taken along line 3-3 in FIG. 2. The processingdevice 10 includes a body 60 that includes a transmissive layer 62 andcontrol layer 64. It may be preferred that the transmissive layer 62 andcontrol layer 64 be attached by a melt bond. As used herein, a “meltbond” is a bond formed by the melting and/or mixing of materials such asthat occurring during, e.g., heat sealing, thermal welding, ultrasonicwelding, chemical welding, solvent bonding, coextrusion, extrusioncasting, etc. In such a bond, the materials facing each other intransmissive layer 62 and control layer 64 must be compatible with meltbonding so that an attachment of sufficient integrity can be formed towithstand the forces experienced during processing of sample materialsin the process chambers.

Alternatively, the transmissive layer 62 and control layer 64 may beattached to each other using, e.g., adhesives, combinations of meltbonding and adhesives, etc. Examples of some attachment techniques maybe described in, e.g., International Publication No. WO 02/01180.

The transmissive layer 62 is preferably constructed of one or morematerials such that the transmissive layer 62 transmits significantportions of selected light. For the purposes of the present invention,significant portions may be, e.g., 50% or more of normal incidentselected light, more preferably 75% or more of normal incident selectedlight. As discussed above, the selected light may be light of one ormore particular wavelengths, one or more ranges of wavelengths, one ormore polarization states, or combinations thereof. Examples of somesuitable materials for the transmissive layer 62 include, but are notlimited to, e.g., polypropylenes, polyesters, polycarbonates,polyethylenes, polypropylene-polyethylene copolymers, cyclo-olefinpolymers (e.g., polydicyclopentadiene), etc.

The control layer 64 is preferably constructed of one or more materialssuch that the control layer 64 blocks significant portions of selectedlight. For the purposes of the present invention, significant portionsof blocked light may be, e.g., 50% or more of normal incident selectedlight, more preferably 75% or more of normal incident selected light,and even more preferably 90% or more of normal incident selected light.As discussed above, the selected light may be one or more particularwavelengths, one or more ranges of wavelengths, one or more polarizationstates, or combinations thereof. Examples of some suitable materials forthe control layer 64 include, but are not limited to, e.g.,polypropylenes, polyesters, polycarbonates, polyethylenes,polypropylene-polyethylene copolymers, cyclo-olefin polymers (e.g.,polydicyclopentadiene), etc., that have been modified to provide thedesired light blocking function. For example, the material used for thecontrol layer 64 may include a light blocking filler (e.g., colorants,carbon black, metallic particles, etc.) to prevent or reducetransmission of selected light through the control layer 64. In otherinstances, the control layer 64 may include a coating or other treatmentthat provides the desired light blocking function.

Where a melt bond between transmissive layer 62 and control layer 64 isto be formed, it may be preferred that the transmissive layer 62 and thecontrol layer 64 be formed of compatible materials, in some instances,it may be preferred that the transmissive layer 62 and the control layer64 be formed of the same polymeric material.

The processing device 10 includes process chambers 50 and a main conduit40 located between the body 60 and the cover sheet 70. Cover sheet 70 isattached to the surface 65 of the control layer 64 facing away from thetransmissive layer 62 using adhesive 72. The cover sheet 70 may,however, be attached to the control layer 64 by any suitable techniqueor combination of techniques, e.g., adhesives, combinations of meltbonding and adhesives, etc. Examples of some suitable attachmenttechniques may be described in, e.g., International Publication No. WO02/01180.

The process chambers 50 are, in the depicted embodiment, defined byprocess chamber structures formed in the control layer 64 of the body 60and the cover sheet 70 attached to the control layer 64. In the depictedembodiment, the process chamber structures are in the form of voidsformed through the control layer 64, the voids including interior sidesurfaces 52. An interior window surface 54 is also formed within theprocess chamber 50 by a portion of the transmissive layer 62 exposed bythe void in the control layer 64. As such, the process chambers 50 maybe described as having a height measured from the cover sheet 70 to theinterior window surface 54. Furthermore, it may be preferred that thecontrol layer 64 have a thickness between the cover sheet 70 and thetransmissive layer 62 that is less than or equal to the height of eachprocess chamber 50. If the height of the process chamber 50 is greaterthan the thickness of the control layer 64, the transmissive layer 62may preferably be thinned or otherwise deformed in the area of thewindow surface 54.

Although the depicted process chamber structure is formed as a void thatexposes a portion of the transmissive layer 62 within the interiorwindow surface 54, it should be understood that, in some instances, itmay be acceptable if a relatively thin portion of the control layer 64remains in the area occupied by the window surface 54. Any suchrelatively thin portion of the control layer 64 should, however, besufficiently thin such that transmission of the selected light throughthe window surface 54 is still possible.

The process chamber structure also preferably includes one or moreinterior side surfaces 52 as depicted that are formed by the controllayer 64. The interior side surfaces 52 may take any suitable shape,although it may be preferred that they extend from one major surface ofthe control layer 64 to the opposite major surface of the control layer64.

FIG. 3 also depicts that the process chambers 50 may include a reagent58 located therein. It may be preferred that at least some, andpreferably all, of the process chambers 50 in the devices 10 of thepresent invention contain at least one reagent before the cover sheet 70is attached to the body 60. The reagent 58 may be fixed within theprocess chamber 50 as depicted in FIG. 3 or it may be loose within theprocess chamber 50. The reagent 58 is optional, i.e., sample processingdevices 10 of the present invention may or may not include any reagents58 in the process chambers 50. In another variation, some of the processchambers 50 may include a reagent 58, while others do not. In yetanother variation, different process chambers 50 may contain differentreagents (in which case it may be desirable to fix the reagents to asurface within each process chamber 50). Further, the interior of theprocess chamber structures may be coated or otherwise processed tocontrol the adhesion of reagents 58. Also, in some instances, reagentsmay be provided on the cover sheet 70.

Although the cover sheet 70 is depicted as generally flat, it should beunderstood that the cover sheet 70 may deviate from a flat sheet if sodesired. For example, the cover sheet 70 may be formed to increase ordecrease the volume of the process chamber 50.

The cover sheet 70 may be provided as, e.g., a sheet of metal foil,polymeric material, multi-layer composite, etc. that is attached to thecontrol layer 64 over the process chamber structures 52 to form processchambers 50. Although the cover sheet 70 is depicted as a unitaryhomogenous layer, it should be understood that the cover sheet 70 mayinclude one or materials and those materials may be provided indifferent layers or they may be intermixed within the cover sheet 70.

If the cover sheet 70 includes a metallic foil, the cover sheet 70 maypreferably include a passivation layer on the surfaces that face theinteriors of the process chambers 50 and main conduit 40 to preventcontamination of the sample materials by the metal. As an alternative toa separate passivation layer, any adhesive layer 72 used to attached thecover sheet 70 to the control layer 64 may also serve as a passivationlayer to prevent contact between the sample materials and any metalliclayer in the cover sheet 70. The cover sheet 70 may preferably bedeformable such that the main conduits 40 can be closed or sealed asdescribed in, e.g., International Publication No. WO 02/01180.

In some embodiments, it may be preferred that the cover sheet 70 andadhesive 72 (if present) provide a reflective surface facing theinterior of the process chambers 50 for the selected light. Thereflectivity may be provided by, e.g., a metallic surface of the coversheet 70, by the adhesive 72 itself, or by a reflective polymeric sheetused to form the cover sheet 70, or any other reflective structure ormaterial.

In other embodiments, it may be preferred that the cover sheet 70 betransmissive such that it transmits the selected light. In such anembodiment, the process chambers 50 may be interrogated by light thatmay be absorbed by one or more components within the process chamber 50.If both the transmissive layer 62 and the cover 70 are transmissive tothe selected light, a detector could be positioned on the side of theprocessing device opposite from the side at which the selected light isdirected into the process chamber 50. For example, if the selected lightis directed into the process chamber 50 through the transmissive layer62, the detector may be placed on the same side as the cover 70 suchthat the selected light is either absorbed within the process chamber 50or transmitted through the transmissive layer 62, process chamber 50 andcover 70 before reaching the detector. Such absorption may be used todetermine the presence or absence of one or more analytes within theprocess chamber 50. Alternatively, signal light from, e.g.,chemiluminescence in the process chamber 50 may be transmitted out ofthe process chamber 50 through either the transmissive layer 62 or thetransmissive cover 70.

A variety of adhesives 72 may be used, although any adhesive selectedshould be capable of withstanding the forces generated during processingof any sample materials located in the process chambers 50, e.g., forcesdeveloped during distribution of the sample materials, forces developedduring thermal processing of the sample materials, etc. Those forces maybe large where, e.g., the processing involves thermal cycling as in,e.g., polymerase chain reaction and similar processes. It may also bepreferred that any adhesives used in connection with the sampleprocessing devices exhibit low fluorescence, be compatible with theprocesses and materials to be used in connection with sample processingdevices, e.g. PCR, etc.

It may be preferred to use adhesives that exhibit pressure sensitiveproperties. Such adhesives may be more amenable to high volumeproduction of sample processing devices since they typically do notinvolve the high temperature bonding processes used in melt bonding, nordo they present the handling problems inherent in use of liquidadhesives, solvent bonding, ultrasonic bonding, and the like. Techniquesfor identifying and selecting pressure sensitive adhesives are discussedin, e.g., International Publication No. WO 02/01180.

It may be preferred that the pressure sensitive adhesives used inconnection with the sample processing devices of the present inventioninclude materials which ensure that the properties of the adhesive arenot adversely affected by water. For example, the pressure sensitiveadhesive will preferably not lose adhesion, lose cohesive strength,soften, swell, or opacify in response to exposure to water during sampleloading and processing. Also, the pressure sensitive adhesive should notcontain any components which may be extracted into water during sampleprocessing, thus possibly compromising the device performance.

In view of these considerations, it may be preferred that the pressuresensitive adhesive be composed of hydrophobic materials. As such, it maybe preferred that the pressure sensitive adhesive be composed ofsilicone materials. Some suitable compositions may be described inInternational Publication WO 00/68336 titled SILICONE ADHESIVES,ARTICLES, AND METHODS (Ko et al.).

Also depicted in the embodiment of FIG. 3 is a cross-sectional view ofthe main conduit 40 that is in fluid communication with the processchambers 50. The main conduit 40, in the depicted embodiment, is definedby conduit structure 44 formed in the control layer 64 of the body 60and the cover sheet 70 attached to the control layer 64. In the depictedembodiment, the conduit structure 44 is in the form of a channel formedinto the surface of the control layer 64 facing away from thetransmissive layer 62. As such, the conduit structure 44 may bedescribed as having a height measured from the cover sheet 70 towardsthe transmissive layer 62. Furthermore, it may be preferred that theheight of the conduit structure 44 be less than the thickness of thecontrol layer 64 (as measured between the opposing major surfaces of thecontrol layer 64) such that, e.g., none of the transmissive layer 62 beexposed within the conduit structure 44.

Although the cover sheet 70 is depicted as generally flat, it should beunderstood that the cover sheet 70 may deviate from a flat sheet if sodesired. For example, the cover sheet 70 may be formed to increase ordecrease the cross-sectional area of the conduit 40 (in the view as seenin FIG. 3).

Further, it may be preferred that the shape of the conduit structure 44and the materials selected for the control layer 64, the cover sheet 70and the adhesive 72 be such that the conduit 40 can be sealed oroccluded by deforming the cover sheet 70 into the conduit structure 44as described in, e.g., International Publication No. WO 02/01180.

FIG. 4 depicts an alternative construction for a sample processingdevice according to the present invention. The processing device isformed by a body 160 and a cover sheet 170. In this embodiment, however,the body 160 is preferably formed of a material or materials that blockthe transmission of selected light between the process chambers 150.

Transmission of the selected light into and/or out of the processchambers 150 occurs, instead, through the cover sheet 170 whichpreferably transmits significant portions of the selected light. For thepurposes of the present invention, significant portions may be, e.g.,50% or more of normal incident selected light, more preferably 75% ormore of normal incident selected light. As discussed above, the selectedlight may be one or more particular wavelengths, one or more ranges ofwavelengths, one or more polarization states, or combinations thereof.Examples of some suitable materials for the cover sheet 170 include, butare not limited to, e.g., polypropylenes, polyesters, polycarbonates,polyethylenes, polypropylene-polyethylene copolymers, cyclo-olefinpolymers (e.g., polydicyclopentadiene), etc.

Although the cover sheet 170 is depicted as a unitary homogenous layer,it should be understood that the cover sheet 170 may include one ormaterials and those materials may be provided in different layers orthey may be intermixed within the cover sheet 170.

The body 160 is preferably constructed of one or more materials suchthat the body 160 blocks transmission of significant portions ofselected light. For the purposes of the present invention, significantportions of blocked light may be, e.g., 50% or more of normal incidentselected light, more preferably 75% or more of normal incident selectlight, and even more preferably 90% or more of normal incident selectedlight. As discussed above, the selected light may be one or moreparticular wavelengths, one or more ranges of wavelengths, one or morepolarization states, or combinations thereof.

Examples of some suitable materials for the body 160 include, but arenot limited to, e.g., polypropylenes, polyesters, polycarbonates,polyethylenes, polypropylene-polyethylene copolymers, cyclo-olefinpolymers (e.g., polydicyclopentadiene), etc., that have been modified toprovide the desired light blocking function. For example, the materialused for the body 160 may include a light blocking filler (e.g.,colorants, carbon black, metallic particles, etc.) to prevent or reducetransmission of selected light through the body 160. In other instances,the body 160 may include a coating or other treatment that provides thedesired light blocking function.

The processing device includes process chambers 150 and a main conduit140 located between the body 160 and the cover sheet 170. The processchambers 150 are, in the depicted embodiment, defined by process chamberstructures 152 formed in the surface 161 of body 160 and the cover sheet170 attached to the body 160. In the depicted embodiment, the processchamber structures 152 are in the form of depressions formed into thebody, but not through the entire thickness of the body 160. Although thecover sheet 170 is depicted as generally flat, it should be understoodthat the cover sheet 170 may deviate from a flat sheet if so desired.For example, the cover sheet 170 may be formed to increase or decreasethe volume of the process chamber 150.

Cover sheet 170 is attached to the surface 161 of the body 160 usingadhesive 172. The cover sheet 170 may, however, be attached to the body160 by any suitable technique or combination of techniques, e.g.,adhesives, combinations of melt bonding and adhesives, etc. Examples ofsome suitable attachment techniques may be described above with respectto adhesive 72 on cover sheet 70 in FIG. 3, as well as in, e.g.,International Publication No. WO 02/01180.

Also depicted in the embodiment of FIG. 4 is a cross-sectional view ofthe main conduit 140 that is in fluid communication with the processchambers 150. The main conduit 140, in the depicted embodiment, isdefined by conduit structure 144 formed in the body 160 and the coversheet 170 attached to the body 160. In the depicted embodiment, theconduit structure 144 is in the form of a channel formed into thesurface 161 facing the cover sheet 170. As such, the conduit structure144 may be described as having a height measured from the cover sheet170 towards the opposing surface 163 of the body 160. Furthermore, itmay be preferred that the height of the conduit structure 144 be lessthan the thickness of the body 160 as measured between opposite majorsurfaces 161 and 163.

The processing devices of the present invention may be manufactured by avariety of methods and techniques. A portion of one exemplarymanufacturing method is depicted in FIG. 5 for manufacturing processingdevices including a body having a transmissive layer and control layeras described in connection with FIG. 3. A melt-processable polymer forthe transmissive layer 62 is delivered from an extruder 80 tomulti-layer feedblock and film die 82. At the same time, amelt-processable polymer for the control layer 64 is delivered fromextruder 84 the multi-layer feedblock and film die 82. The twomelt-processable polymers streams are delivered to the multi-layerfeedblock and film die 82 at or above their melt-processing temperature.The multi-layer feedblock and film die 82 preferably keeps the twopolymer melt streams from extruders 80 and 84 separated such that thetwo polymers form separate and discrete layers 62 and 64.

The layers 62 and 64 of polymer are discharged from the multi-layerfeedblock and film die 82 onto a forming tool 86. It may be preferredthat the polymers be drop cast onto the surface of the forming tool 86at a point near the nip between forming tool 86 and backup roll 88.

The forming tool 86 includes protrusions 87 extending therefrom thatcorrespond to the various features to be formed in the processingdevices, e.g., process chambers, conduits, etc. It may be preferred thatthe thickness of each of layers 62 and 64 be controlled such that thethickness of layer 64 is less than or equal to the height of theprotrusions 87 that form the process chamber structures in theprocessing devices of the present invention. Limiting the thickness oflayer 64 in that manner can provide for process chamber structures inlayer 64 that are formed as voids as described above with respect toFIG. 3.

It may be preferred that at least the control layer 64 be delivered tothe forming tool 86 at a temperature that is at or above its meltprocessing temperature (i.e., the temperature at which it can be formedor molded). By providing the control layer 64 to the forming tool 86 ator above its melt processing temperature, the polymer in the controllayer can adequately form or be replicated to the shape of theprotrusions 87 on the forming tool 86. Although the forming tool 86 isdepicted as a roll, it should be understood that it may alternatively beprovided as a continuous belt or other structure amenable to continuousweb-form processing.

It may also be preferred that the polymer of the transmissive layer 62also be delivered to the nip formed by forming tool 86 and backup roll88 at a temperature that is at or above its melt processing temperaturesuch that the two layers 62 and 64 can be formed together to provide amelt bond between the two layers while the features of forming tool 86are being formed into the control layer 64.

The temperatures of both layers 62 and 64 are preferably lowered tobelow their respective melt processing temperatures at some point afterthe nip with backup roll 88 to retain the structures formed in layer 64and provide mechanical stability to the web.

The result of the processing depicted in FIG. 5 is a web including botha transmissive layer 62 and control layer 64 to form the body 60 of aprocessing device according to the present invention. The control layer64 includes structures formed therein for, e.g., process chambers,conduits, loading chambers, etc.

FIG. 6 is a schematic diagram of the larger process for manufacturingprocessing devices according to the present invention. The systemdepicted in FIG. 6 includes the components and process of FIG. 5 asapparatus 89. The web formed by apparatus 89 (including the transmissivelayer and the control layer 64) may preferably be fed into a reagentstation 90 where reagents can be added to, e.g., the process chamberstructures as discussed herein. Following the addition of reagents, theweb may preferably be fed into a laminating station 91 where a coversheet web 70 is laminated thereto to form a composite web structureincluding process chambers 50, conduits 40, etc. The composite web maythen preferably be delivered to a sheeting station 92 where the web isseparated by, e.g., die cutting, into individual processing devices 10.

FIGS. 7 & 8 depict an alternative manufacturing process that may be usedto, e.g., manufacture processing devices constructed as described inFIG. 4. The A melt-processable polymer for the body 160 is deliveredfrom an extruder 180 to die 182. The melt-processable polymer stream isdelivered to the die 182 at or above its melt-processing temperature.

The polymer layer 160 is discharged from the die 182 onto a forming tool186. It may be preferred that the layer 160 be drop cast onto theforming tool 186 just before the nip formed with backup roll 188. Theforming tool 186 includes protrusions 187 extending therefrom thatcorrespond to the various features to be formed in the processingdevices, e.g., process chambers, conduits, etc. It is preferred that thethickness of the polymer layer 160 be controlled such that the thicknessof layer 160 is greater than the height of the protrusions 187 that formthe process chamber structures in the processing devices of the presentinvention.

It may be preferred that the polymer layer 160 be delivered to theforming tool 186 at a temperature that is at or above its meltprocessing temperature (i.e., the temperature at which it can be formedor molded). By providing the polymer layer 160 to the forming tool 186at or above its melt processing temperature, the polymer can adequatelyform or be replicated to the shape of the protrusions 187 on the formingtool 186. Although the forming tool 186 is depicted as a roll, it shouldbe understood that it may alternatively be provided as a continuous beltor other structure amenable to continuous web-form processing.

The temperature of the polymer layer 160 is preferably lowered to belowthe melt processing temperature at some point after the nip with backuproll 188 to retain the structures formed in layer 160 and providemechanical stability to the web. The result of the processing depictedin FIG. 7 is a web 160 that can be used to form the bodies of processingdevices according to the present invention. The web 160 includesstructures formed therein for, e.g., process chambers, conduits, loadingchambers, etc.

FIG. 8 is a schematic diagram of the larger process for manufacturingprocessing devices according to the present invention. The systemdepicted in FIG. 8 includes the components and process of FIG. 7 asapparatus 189. The web formed by apparatus 189 may preferably be fedinto a reagent station 190 where reagents can be added to, e.g., theprocess chamber structures as discussed herein. Following the additionof reagents, the web may preferably be fed into a laminating station 191where a cover sheet web 170 is laminated thereto to form a composite webstructure including process chambers, conduits, etc. The composite webmay then preferably be delivered to a sheeting station 192 where the webis separated by, e.g., die cutting, into individual processing devices110.

In an alternative process, the web formed by apparatus 189 may besheeted before any reagents are added to the sheeted web. It may also bepreferred that in such a process, the cover sheet web 170 be sheetedbefore it is laminated to the sheets formed from the web of apparatus189.

All references and publications cited herein are expressly incorporatedherein by reference in their entirety into this disclosure. Illustrativeembodiments of this invention are discussed and reference has been madeto possible variations within the scope of this invention. These andother variations and modifications in the invention will be apparent tothose skilled in the art without departing from the scope of theinvention, and it should be understood that this invention is notlimited to the illustrative embodiments set forth herein. Accordingly,the invention is to be limited only by the claims provided below andequivalents thereof.

1. A sample processing device comprising: a body comprising atransmissive layer that transmits selected light and a control layerthat blocks the selected light, wherein the control layer is attached tothe transmissive layer with a first major surface of the control layerfacing the transmissive layer and a second major surface facing awayfrom the transmissive layer; a plurality of process chamber structuresformed in the control layer, wherein each of the process chamberstructures comprises an interior window surface and an interior sidesurface formed by the control layer; a cover sheet attached to thesecond major surface of the control layer, wherein the cover sheet andthe plurality of process chamber structures define a plurality ofprocess chambers in the sample processing device, wherein the selectedlight can be transmitted into or out of each process chamber through theinterior window surface; and a conduit in the sample processing device,wherein each process chamber of the plurality of process chambers is influid communication with the conduit.
 2. A device according to claim 1,wherein each of the process chamber structures comprises a void formedthrough the first major surface and the second major surface of thecontrol layer, wherein the void exposes the interior window surfaceformed by the transmissive layer.
 3. A device according to claim 1,wherein the interior window surface within each process chamber isformed by the transmissive layer.
 4. A device according to claim 1,wherein the control layer is melt-bonded to the transmissive layer.
 5. Adevice according to claim 1, wherein the transmissive layer and thecontrol layer comprise the same polymeric material, and further whereinthe control layer comprises a light blocking filler incorporatedtherein.
 6. A device according to claim 1, wherein each process chamberof the plurality of process chambers comprises a height measured fromthe cover sheet to the interior window surface, and wherein the controllayer comprises a thickness between the cover sheet and the transmissivelayer that is less than or equal to the height of each process chamberof the plurality of process chambers.
 7. A device according to claim 1,wherein the conduit is formed between the cover sheet and the controllayer.
 8. A device according to claim 1, wherein the conduit comprises aconduit structure formed in the second major surface of the controllayer, wherein the cover sheet and the conduit structure define theconduit in the sample processing device.
 9. A device according to claim8, wherein the conduit structure comprises a depth measured from thesecond major surface of the control layer that is less than a thicknessof the control layer as measured between the first major surface and thesecond major surface of the control layer.
 10. A device according toclaim 1, wherein the cover sheet blocks the selected light.
 11. A deviceaccording to claim 1, wherein the cover sheet comprises a reflectivesurface facing the control layer.
 12. A device according to claim 1,wherein the cover sheet transmits the selected light.
 13. A sampleprocessing device comprising: a body comprising a transmissive layerthat transmits selected light and a control layer that blocks theselected light, wherein a first major surface of the control layer facesand is melt-bonded to the transmissive layer, and wherein a second majorsurface of the control layer faces away from the transmissive layer; aplurality of process chamber structures formed in the body, wherein eachof the process chamber structures comprises a void formed through thefirst major surface and the second major surface of the control layer,wherein the void exposes an interior window surface formed by thetransmissive layer within each process chamber structure; a cover sheetattached to the second major surface of the control layer, wherein thecover sheet and the plurality of process chamber structures define aplurality of process chambers in the sample processing device, andwherein the cover sheet blocks the selected light; and a conduit formedbetween the cover sheet and the control layer in the sample processingdevice, wherein each process chamber of the plurality of processchambers is in fluid communication with the conduit.
 14. A method ofmanufacturing a sample processing device, the method comprising:providing a body that comprises: a transmissive layer that transmitsselected light; a control layer that blocks the selected light, whereinthe control layer is attached to the transmissive layer with a firstmajor surface of the control layer facing the transmissive layer and asecond major surface facing away from the transmissive layer; aplurality of process chamber structures formed in the control layer,wherein each of the process chamber structures comprises an interiorwindow surface and an interior side surface formed by the control layer;and attaching a cover sheet to the second major surface of the controllayer, wherein the cover sheet and the plurality of process chamberstructures define a plurality of process chambers in the sampleprocessing device, and wherein attaching the cover sheet forms a conduitin the sample processing device, wherein each process chamber of theplurality of process chambers is in fluid communication with theconduit.
 15. A method according to claim 14, wherein providing the bodycomprises melt bonding the control layer to the transmissive layer. 16.A method according to claim 14, wherein providing the body comprisesforming a void through the control layer to form each process chamberstructure of the plurality of process chamber structures, whereinforming the void exposes the interior window surface of the processchamber.
 17. A method according to claim 16, wherein, for each processchamber structure, forming the void comprises exposing the transmissivelayer to form the interior window surface.
 18. A method according toclaim 14, wherein providing the body comprises forming the plurality ofprocess chamber structures into the control layer.
 19. A methodaccording to claim 20, wherein forming the plurality of process chamberstructures comprises: providing the control layer on the transmissivelayer, wherein the control layer comprises polymeric material at orabove a melt processing temperature of the polymeric material; formingthe plurality of process chamber structures into the control layer whilethe control layer is held at or above the melt processing temperature;and lowering the temperature of the control layer below the meltprocessing temperature after forming the plurality of process chamberstructures.
 20. A method according to claim 14, wherein the conduit isformed between the cover sheet and the control layer.
 21. A methodaccording to claim 14, wherein the conduit comprises a conduit structureformed in the second major surface of the control layer, wherein thecover sheet and the conduit structure define the conduit in the sampleprocessing device.
 22. A method according to claim 21, furthercomprising forming the conduit structure in the second major surface ofthe control layer.
 23. A method according to claim 22, wherein formingthe conduit structure comprises: providing the control layer on thetransmissive layer, wherein the control layer comprises polymericmaterial at or above a melt processing temperature of the polymericmaterial; forming the conduit structure in the control layer while thecontrol layer is held at or above the melt processing temperature; andlowering the temperature of the control layer below the melt processingtemperature after forming the conduit structure.
 24. A method accordingto claim 21, wherein the conduit structure comprises a depth measuredfrom the second major surface of the control layer that is less than athickness of the control layer as measured between the first majorsurface and the second major surface of the control layer.
 25. A methodaccording to claim 14, further comprising locating one or more reagentsin one or more of the process chamber structures before attaching thecover sheet.
 26. A method according to claim 14, wherein each processchamber of the plurality of process chambers comprises a height measuredfrom the cover sheet to the interior window surface, and wherein thecontrol layer comprises a thickness between the cover sheet and thetransmissive layer that is less than or equal to the height of eachprocess chamber of the plurality of process chambers.
 27. A methodaccording to claim 14, wherein the interior window surface within eachprocess chamber is formed by the transmissive layer.
 28. A methodaccording to claim 14, wherein the cover sheet blocks the selectedlight.
 29. A method according to claim 14, wherein the cover sheetcomprises a reflective surface facing the control layer.
 30. A methodaccording to claim 14, wherein the cover sheet transmits the selectedlight.
 31. A sample processing device comprising: a body comprising afirst major surface and a second major surface, wherein the second majorsurface is flat, and wherein the body blocks selected light; a pluralityof process chamber structures formed in the body, wherein the processchamber structures are formed into the first major surface of the body;a cover sheet attached to the first major surface of the body, whereinthe cover sheet and the plurality of process chamber structures define aplurality of process chambers in the sample processing device, andwherein the cover sheet transmits the selected light; and a conduitlocated between the body and the cover sheet, wherein each processchamber of the plurality of process chambers is in fluid communicationwith the conduit.
 32. A device according to claim 31, wherein theconduit comprises conduit structure formed in the first major surface ofthe body, wherein the cover sheet and the conduit structure define theconduit in the sample processing device.
 33. A device according to claim31, wherein the cover sheet is adhesively attached to the first majorsurface of the body.
 34. A method of manufacturing a sample processingdevice, the method comprising: providing a body that comprises a firstmajor surface and a second major surface, wherein the second majorsurface is flat, and wherein the body blocks selected light, wherein thebody further comprises a plurality of process chamber structures formedin the first major surface of the body; and attaching a cover sheet tothe first major surface of the body, wherein the cover sheet and theplurality of process chamber structures define a plurality of processchambers in the sample processing device; and wherein attaching thecover sheet forms a conduit in the sample processing device, whereineach process chamber of the plurality of process chambers is in fluidcommunication with the conduit.
 35. A method according to claim 34,wherein the conduit is formed between the cover sheet and the firstmajor surface of the body.
 36. A method according to claim 34, whereinthe conduit comprises a conduit structure formed in the first majorsurface of the body, wherein the cover sheet and the conduit structuredefine the conduit in the sample processing device.
 37. A methodaccording to claim 34, further comprising forming the conduit structurein the first major surface of the body.
 38. A method according to claim34, further comprising locating one or more reagents in one or more ofthe process chamber structures before attaching the cover sheet.
 39. Amethod according to claim 34, wherein the cover sheet transmits theselected light.